Highly congenic mice with and without mutant genes with clear-cut effects will be used to analyze gene-action leading to at least ten different hereditary anemias (W-locus alleles, Sl-locus alleles, Hertwig's anemia, flexed, microcytic, hemolytic, jaundiced, normoblastic, spherocytic, and sex-linked iron-transport defect). We will study early embryonic stages and follow developmental changes to the full adult stage (60 to 90 days) when available. We will compare responses to hemopoietic stresses (hypoxia, bleeding, phenylhydrazine injection, and whole-body irradiation) and to stimuli such as erythropoietin of adult normal mice and mice with each type of severe hereditary anemia. We will continue to investigate the structural nature and genetic control of hemoglobin polymorphism in normal adult mice of many different inbred strains, testing for relationship to anemias, particularly those with a hemolytic component. We have located the position of the Hba locus between wa-2 and sh-2 in chromosome ll (linkage Group VII). Eventually we hope to be able to test genetically Popp's attractive hypothesis that many mice have duplicated alpha-chains. We will analyze the pleiotropic effects, often pathological, associated with genic substitutions that also cause differences in hair pigmentation.